Vaksin untuk mencegah malaria (pra‐erythrocytic)
Abstract
Background
Vaccines against all stages of the malaria parasite are in development, mainly for Plasmodium falciparum, which causes the most serious form of malaria. Pre‐erythrocytic vaccines act to prevent or delay a malaria attack by attacking the sporozoite and liver stages before the parasite reaches the bloodstream.
Objectives
To assess the efficacy and safety of pre‐erythrocytic malaria vaccines against any type of human malaria.
Search methods
In March 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and the Science Citation Index. We also searched conference proceedings and reference lists of articles, and contacted organizations and researchers in the field.
Selection criteria
Randomized controlled trials comparing pre‐erythrocytic vaccines with placebo, control vaccine, or routine antimalarial control measures in people of any age receiving an artificial challenge or natural exposure to malaria infection.
Data collection and analysis
Both authors independently assessed trial quality and extracted data. Results of meta‐analyses were expressed as risk ratios with 95% confidence intervals (CI) using an intention‐to‐treat analysis.
Main results
Nine safety and efficacy trials, and two safety trials, with over 3000 participants were included. In semi‐immune children, RTS,S vaccine reduced clinical episodes of malaria by 26% (95% CI 13% to 37%) and severe malaria by 58% (95% CI 15% to 79%) for up to 18 months. Prevalence of parasitaemia was also reduced by 26% (95% CI 11% to 38%) at six months after immunization. RTS,S also reduced clinical malaria episodes by 63% (95% CI 18% to 83%) in semi‐immune adult men in the second year of follow up after a booster dose. No severe adverse events were judged to be related to RTS,S vaccine, although the frequencies of injection site pain, swelling, arm motion limitation, headache, and malaise were increased in the vaccine groups. There was no evidence for effect of the CS‐NANP vaccines (307 participants, 3 trials), CS102 peptide vaccine (14 participants, 1 trial), or the ME‐TRAP vaccine (372 participants, 1 trial).
Authors' conclusions
RTS,S vaccine was effective in preventing a significant number of clinical malaria episodes, including good protection against severe malaria in children for 18 months. No severe adverse events were attributable to the vaccine. Progression of this vaccine towards licensing is justified while efforts to increase its efficacy continue. The other vaccines do not look promising and further research is a priority.
PICO
Plain language summary
Vaksin untuk mencegah malaria dalam fasa pra‐erythrocytic
Malaria adalah penyakit parasit yang disebarkan oleh nyamuk. Ia menjejaskan berjuta‐juta orang di seluruh dunia dan merupakan punca utama penyakit dan kematian. Gejala malaria tanpa komplikasi termasuk demam, sakit kepala, sakit otot, dan muntah; dan kanak‐kanak biasanya juga mengalami pernafasan yang cepat, batuk, dan sawan. Malaria yang teruk membawa kepada pengsan dan kematian. Malaria tanpa komplikasi hampir selalu boleh disembuhkan dengan ubat yang sesuai, diberikan sejurus selepas gejala muncul, tetapi pada kanak‐kanak kecil khususnya, keterukan dan kematian boleh datang dalam masa 48 jam. Harapan − disokong oleh penyelidikan berdekad‐dekad yang semakin bertambah baik − kekal bahawa satu atau lebih vaksin untuk mencegah malaria akan menambah kepada alat kawalan malaria sedia ada. Jangkaan adalah bahawa vaksin yang berkesan akan mengurangkan kejadian malaria, tetapi kerana kerumitan organisma dan faktor lain, perlindungan tidak akan lengkap. Parasit malaria berkembang melalui beberapa fasa dalam tubuh manusia yang menimbulkan tindak balas imunologi yang berbeza, dan vaksin untuk semua fasa sedang dalam pembangunan. Ulasan ini melihat kepada vaksin yang disasarkan pada fasa 'pra‐erythrocytic' dalam kehidupan parasit, iaitu fasa sebelum parasit mula‐mula memasuki aliran darah dari hati. Kajian empat jenis vaksin terhadap P. falciparum, spesies malaria manusia yang paling penting, telah tersedia untuk ulasan ini. Salah satu daripada ini (vaksin RTS,S) mengurangkan dengan ketara bilangan episod malaria klinikal dan malaria teruk dalam kanak‐kanak, manakala tiga vaksin lain adalah tidak berkesan di bawah syarat‐syarat kajian. Tiada peristiwa buruk yang teruk diperhatikan selepas vaksinasi RTS,S dinilai berkaitan dengan vaksinasi, namun peristiwa buruk yang kecil seperti sakit kepala, bengkak, dan rasa lesu adalah berkaitan dengan vaksinasi.
